The transdermal route of parenteral delivery of drugs provides many advantages, and transdermal systems for delivering a wide variety of drugs or other beneficial agents are described in U.S. Pat. Nos. 3,598,122, 3,598,123, 4,379,454, 4,286,592, 4,314,557 and 4,568,343, for example, all of which are incorporated herein by reference. In many cases, drugs which would appear to be ideal candidates for transdermal delivery are found to have such low permeability through intact skin that they cannot be delivered in therapeutically effective amounts from reasonably sized devices.
The terms "therapeutically effective rate" and "therapeutically effective amount", as used herein, refer to a rate or an amount of drug or other agent which provides a therapeutic effect or result.
The term "reasonable size", as used herein, refers to a device of a size with a base surface area (that area in contact with the skin site) that is from about 1 cm.sup.2 to about 50 cm.sup.2, preferably from about 5 cm.sup.2 to about 25 cm.sup.2. While devices of as large as 200 cm.sup.2 can be considered to be of "conventional" size, such large sizes are not generally acceptable to people, as a practical matter.
In an effort to increase skin permeability so that drugs can be delivered in therapeutically effective amounts, it has been proposed to pretreat the skin with various chemicals or to concurrently deliver the drug in the presence of a permeation enhancer. Various materials have been suggested for this purpose as described in U.S. Pat. Nos. 4,299,826, 4,343,798, 4,046,886, 4,130,643, 4,405,616, 4,335,115, 4,130,667, 3,903,256, 4,379,454, 3,527,864, 3,952,099, 3,896,238, 3,472,931, 4,788,062, 4,746,515, 4,863,738 and 4,863,970; British Pat. No. 1,011,949; and Idson, "Percutaneous Absorption," J. Pharm. Sci. (1975) 64:901-924.
It is often difficult to predict which compounds will work as permeation enhancers and which permeation enhancers will work for particular drugs. In systemic drug delivery applications, a compound that enhances the permeability of one drug or a family of drugs may not necessarily enhance the permeability of another drug or family of drugs. Therefore, the usefulness of a particular compound as a permeation enhancer must be analyzed carefully.